RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:NK Cell-Based Immunotherapy: Pioneering a New Era in Cancer Treatment.
NK Cell-Based Immunotherapy: Pioneering a New Era in Cancer Treatment.
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自然杀伤(NK)细胞是先天免疫系统的重要细胞毒性效应细胞,在癌症免疫治疗中具有显著优势,主要源于其固有的非MHC限制性细胞毒作用及不依赖抗原的肿瘤识别能力。与T细胞免疫疗法相比,以NK细胞为核心的策略可通过嵌合抗原受体(CAR)工程化实现精准免疫治疗,并具有更好的异体相容性。NK细胞天然不易导致移植物抗宿主病(GVHD),因此可绕开自体细胞来源限制,实现“现货型”治疗。本综述系统介绍NK细胞发育生物学和功能特征、多样化细胞来源,以及由活化和抑制性受体平衡调控的动态机制。此外,文章重点介绍工程化NK细胞疗法(包括CAR-NK)的近期临床转化进展,并讨论其在癌症治疗中的应用。
Natural killer (NK) cells are essential cytotoxic effectors of the innate immune system with significant therapeutic advantages in cancer immunotherapy, primarily due to their intrinsic MHC-unrestricted cytotoxicity and capacity for antigen-independent tumor recognition. Compared to T cell-based immunotherapies, NK cell-centered strategies facilitate precision immunotherapy through chimeric antigen receptor (CAR) engineering while demonstrating superior allogeneic compatibility.
This inherent resistance to graft-versus-host disease (GVHD) circumvents the limitations of autologous cell sourcing and enables "off-the-shelf" therapeutic availability. This review systematically outlines the developmental biology and functional characteristics of NK cells, their diverse cellular origins, and the dynamic regulatory mechanisms governed by the balance of activating and inhibitory receptors.
Furthermore, it highlights recent advances in the clinical translation of engineered NK cell therapies, including CAR-NK cells, and discusses their therapeutic applications in cancer treatment.
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